Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain
Article first published online: 5 MAR 2013
Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 3, pages 384–396, March 2013
How to Cite
Xing, F., Kobayashi, A., Okuda, H., Watabe, M., Pai, S. K., Pandey, P. R., Hirota, S., Wilber, A., Mo, Y.-Y., Moore, B. E., Liu, W., Fukuda, K., Iiizumi, M., Sharma, S., Liu, Y., Wu, K., Peralta, E. and Watabe, K. (2013), Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain. EMBO Mol Med, 5: 384–396. doi: 10.1002/emmm.201201623
- Issue published online: 5 MAR 2013
- Article first published online: 5 MAR 2013
- Manuscript Accepted: 18 DEC 2012
- Manuscript Revised: 13 DEC 2012
- Manuscript Received: 1 JUN 2012
- Funded Access
- cancer stem-like cell;
- reactive astrocytes
Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the 1 year survival rate among these patients remains less than 20%. However, the pathological mechanism of brain metastasis is as yet poorly understood. In this report, we found that metastatic breast tumour cells in the brain highly expressed IL-1β which then ‘activated’ surrounding astrocytes. This activation significantly augmented the expression of JAG1 in the astrocytes, and the direct interaction of the reactivated astrocytes and cancer stem-like cells (CSCs) significantly stimulated Notch signalling in CSCs. We also found that the activated Notch signalling in CSCs up-regulated HES5 followed by promoting self-renewal of CSCs. Furthermore, we have shown that the blood-brain barrier permeable Notch inhibitor, Compound E, can significantly suppress the brain metastasis in vivo. These results represent a novel paradigm for the understanding of how metastatic breast CSCs re-establish their niche for their self-renewal in a totally different microenvironment, which opens a new avenue to identify a novel and specific target for the brain metastatic disease.